Safety and Pharmacokinetics of Single and Multiple Dose Rifampin in Infants

The purpose of this study is to learn more about the safety and dosing of rifampin in infants.

Study Overview

• Status: Terminated
• Conditions: Infection
• Intervention / Treatment: Drug: rifampin

Detailed Description

Pharmacokinetics and safety of rifampin will be studied in term and preterm infants who are receiving rifampin per standard of care.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7596
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Cohort 1:

• Suspected systemic infection
• Infant < 121 days of age at the time of 1st dose of rifampin administration
• Sufficient intravascular access (either peripheral or central) to receive rifampin.

Cohort 2:

• Receiving rifampin per local standard of care.
• Infant < 121 days of age at the time of 1st dose of rifampin administration

Exclusion Criteria:

Cohort 1:

• History of allergic reactions to rifampin
• Aspartate aminotransferase (AST) greater than 3 times upper limit of normal
• Alanine aminotransferase (ALT) greater than 3 times upper limit of normal
• Serum creatinine greater than 1.7 mg.dL
• Urine output < 0.5 mL/hr/kg over the prior 24 hours
• Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study

Cohort 2:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: rifampin; Cohort 1 will include infants who will be receiving up to 4 doses rifampin per study protocol.	Drug: rifampin; Infants who will be receiving up to 4 doses of rifampin per protocol(Cohort 1) Cohort 1: Dosing will be as follows: GA at birth < 32 weeks - PNA < 14 days: 10 mg/kg QD GA at birth < 32 weeks - PNA ≥ 14 days: 15 mg/kg QD GA at birth ≥ 32 weeks - PNA < 14 days: 15 mg/kg QD GA at birth ≥ 32 weeks - PNA ≥ 14 days: 20 mg/kg QD
No Intervention: rifampin per standard of care; Cohort 2: Receiving rifampin per standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve 0-24 hours for rifampin	Sampling for 24 hr dosing:Dose 1:0-15min,30-60min,1-3hr,3-6hr, 6-12hr,12-18hr. Dose 2,3 or 4:<15min prior to dose, 48-72hrs. Sampling for 12 hr dosing:Dose 1: 0-15min, 0.5-1hr, 1-2hr, 2-4hr, 5-8hr, 8-10 hr. Dose 2, 3 or 4:<15min prior to dose, 24-36hr
Peak plasma concentration of rifampin	Sampling for 24 hr dosing:Dose 1:0-15min,30-60min,1-3hr,3-6hr, 6-12hr,12-18hr. Dose 2,3 or 4:<15min prior to dose, 48-72hrs. Sampling for 12 hr dosing:Dose 1: 0-15min, 0.5-1hr, 1-2hr, 2-4hr, 5-8hr, 8-10 hr. Dose 2, 3 or 4:<15min prior to dose, 24-36hr
Clearance of rifampin	Sampling for 24 hr dosing:Dose 1:0-15min,30-60min,1-3hr,3-6hr, 6-12hr,12-18hr. Dose 2,3 or 4:<15min prior to dose, 48-72hrs. Sampling for 12 hr dosing:Dose 1: 0-15min, 0.5-1hr, 1-2hr, 2-4hr, 5-8hr, 8-10 hr. Dose 2, 3 or 4:<15min prior to dose, 24-36hr
Volume of distribution at steady state	Sampling for 24 hr dosing:Dose 1:0-15min,30-60min,1-3hr,3-6hr, 6-12hr,12-18hr. Dose 2,3 or 4:<15min prior to dose, 48-72hrs. Sampling for 12 hr dosing:Dose 1: 0-15min, 0.5-1hr, 1-2hr, 2-4hr, 5-8hr, 8-10 hr. Dose 2, 3 or 4:<15min prior to dose, 24-36hr
Half life of rifampin	Sampling for 24 hr dosing:Dose 1:0-15min,30-60min,1-3hr,3-6hr, 6-12hr,12-18hr. Dose 2,3 or 4:<15min prior to dose, 48-72hrs. Sampling for 12 hr dosing:Dose 1: 0-15min, 0.5-1hr, 1-2hr, 2-4hr, 5-8hr, 8-10 hr. Dose 2, 3 or 4:<15min prior to dose, 24-36hr

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events as a measure of safety and tolerability.	From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of rifampin to 7 days after the last dose of rifampin.

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Matthew M. Laughon, MD, MPH, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Estimate): September 14, 2012
• Last Update Submitted That Met QC Criteria: September 13, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: infants; rifampin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: 10-2314; 1K23HD068497-01 (U.S. NIH Grant/Contract)